This proposal will leverage the expertise in HSV-2 and cellular immunology developed at the UW/FHCRC with the state of the art adenovirus delivery platform developed by GenVec to develop an HSV-2, adenovirus vector based vaccine. This phase 1 SBIR application will generate and test in preclinical models initial prototypes of such a vaccine. The specific aims during phase I of the SBIR are to construct and test two adenovirus vectors each containing a HSV-2 viral antigen, UL-47 and UL-19. These antigens have been shown to cause prevalent in CD4+ and CD8+ T cell responses among humans with naturally acquired HSV-2. It is anticipated that the proposed AdHSV-2 vaccine will increase the HSV-2 specific CD8+ T cell responses to the UL-47 and UL-19 antigens in animal models. During phase II of this SBIR we plan to bring these AdHSV-2 vaccines to the IND stage. The long-term goal of this effort is to conduct clinical trials testing whether AdHSV-2 vaccines decrease acquisition of HSV-2 and/or decrease viral reactivation as measured by frequency and titer of viral shedding and lessened rate of recurrent episodes. PUBLIC HEALTH RELEVANCE: The HSV-2 epidemic has continued to spread throughout the world and seroprevalence rates have climbed to 30-50%. There is a strong association between antecedent HSV-2 infection and increased risk of HIV acquisition. Antiviral therapy to reduce transmission of HSV-2 to sexual partners is only partially successful. No effective HSV-2 vaccine is currently available. Evidence has accumulated on the importance that HSV-2 specific CD8+ T cells play in control of latency and reactivation of HSV-2 infections in humans. Concomitant with these studies of HSV-2 immunobiology has been the recent demonstration in humans that recombinant adenovirus vectors elicit high frequency of HIV CD8+ T cell responses. This proposal will leverage the expertise in HSV-2, and cellular immunology developed in the laboratories of Drs. L. Corey and D. Koelle with the state of the art adenovirus delivery platform developed by GenVec to develop an HSV-2, Ad5 based vaccine.